SARS-CoV-2 Induces Cytokine Responses in Human Basophils.

Basophils play a key role in the orientation of immune responses. Though the interaction of SARS-CoV-2 with various immune cells has been relatively well studied, the response of basophils to this pandemic virus is not characterized yet. In this study, we report that SARS-CoV-2 induces cytokine responses and in particular IL-13, in both resting and IL-3 primed basophils. The response was prominent under IL-3 primed condition. However, either SARS-CoV-2 or SARS-CoV-2-infected epithelial cells did not alter the expression of surface markers associated with the activation of basophils, such as CD69, CD13 and/or degranulation marker CD107a. We also validate that human basophils are not permissive to SARS-CoV-2 replication. Though increased expression of immune checkpoint molecule PD-L1 has been reported on the basophils from COVID-19 patients, we observed that SARS-CoV-2 does not induce PD-L1 on the basophils. Our data suggest that basophil cytokine responses to SARS-CoV-2 might help in reducing the inflammation and also to promote antibody responses to the virus.

Boolean analysis of the transcriptomic data to identify novel biomarkers of IVIG response.

Intravenous immunoglobulin (IVIG) is used to treat several autoimmune and inflammatory diseases, but some patients are refractory to IVIG and require alternative treatments. Identifying a biomarker that could segregate IVIG responders from non-responders has been a subject of intense research. Unfortunately, previous transcriptomic studies aimed at addressing IVIG resistance have failed to predict a biomarker that could identify IVIG-non-responders. Therefore, we used a novel data mining technique on the publicly available transcriptomic data of Kawasaki disease (KD) patients treated with IVIG to identify potential biomarkers of IVIG response. By studying the boolean patterns hidden in the expression profiles of KD patients undergoing IVIG therapy, we have identified new metabolic pathways implicated in IVIG resistance in KD. These pathways could be used as biomarkers to segregate IVIG non-responders from responders prior to IVIG infusion. Also, boolean analysis of the transcriptomic data could be further extended to identify a universal biomarker that might predict IVIG response in other autoimmune diseases.

Interplay between Liver X Receptor and Hypoxia Inducible Factor 1α Potentiates Interleukin-1ß Production in Human Macrophages.

Low-grade inflammation is constitutive of atherosclerosis, and anti-inflammatory therapy inhibiting interleukin-1ß (IL-1ß) reduces the rate of cardiovascular events. While cholesterol accumulation in atheroma plaque and macrophages is a major driver of the inflammatory process, the role of the LXR cholesterol sensors remains to be clarified. Murine and human macrophages were treated with LXR agonists for 48 h before Toll-like receptor (TLR) stimulation. Unexpectedly, we observe that, among other cytokines, LXR agonists selectively increase IL1B mRNA levels independently of TLR activation. This effect, restricted to human macrophages, is mediated by activation of HIF-1α through LXR. Accordingly, LXR agonists also potentiate other HIF-1α-dependent pathways, such as glycolysis. Treatment of human macrophages with carotid plaque homogenates also leads to induction of IL1B in an LXR-dependent manner. Thus, our work discloses a mechanism by which cholesterol and oxysterols trigger inflammation in atherosclerosis. This suggests perspectives to target IL-1ß production in atherosclerotic patients.